Julia All Cardio Combined

What are the names of the 4 lipoproteins we covered in class?

chylomicrons, very low-density lipoproteins, low-density lipoproteins, high-density lipoproteins

Why are lipoproteins necessary and what is their general function?

They are necessary for transporting lipids through the systemic circulation because they are water ___.

insoluble

What is the general structure of a lipoprotein?

-hydrophobic core is made up of ___ and __ ___

triglycerides, cholesterol ester

What is the general structure of a lipoprotein?

-hydrophilic surface has ___, free __, and __

phospholipids, cholesterol, apolipoprotein

Dietary triglycerides and fat are digested by pancreatic lipase and co-lipase, and formed into ___ with the aid of bile salts.

micelles

Dietary triglycerides and fat are able to move through GIF towards enterocytes where they can be passively absorbed or actively transported across the ___ into enterocytes

NPC1L1

Inside the enterocytes of the small intestine, what vesicular-like structure are these dietary lipids (cholesterol and tg) packaged in?

chylomicrons

What apolipoprotein are these dietary lipids (cholesterol and tg) tagged with?

B48

Through what system do chylomicrons travel through prior to making their way to the systemic

circulation?

lymphatic

Through what structure do chylomicrons enter the blood stream?

thoracic duct

What proteins do chylomicrons receive from HDL once they are in the bloodstream?

Apo-E, Apo-Cii

What is the function of Apo-Cii in relation to chylomicrons?

It activates __ __ (LPL) to breakdown TG-->glycerol+FFA

lipoprotein lipase

Once the function of Apo-Cii is carried out, what happens to it?

it is returned to HDL

Do chylomicrons change in size after interaction with lipoprotein lipase?

Yes

What are the remaining molecules called after chylomicrons decrease in size?

chylomicron remnant

What is the function of ApoE?

allows for high affinity binding of chylomicron remnants to __ __

LDL receptor

What happens to chylomicrons once they bind to the LDL receptor?

-They are __ into liver, where they are broken down and their contents can be recycled in further lipoprotein metabolism

endocytosed

What lipoprotein does the liver package mainly triglycerides into and release into the circulation?

VLDL

What apolipoproteins do VLDL carry?

B100, Apo-Cii, Apo-E

the apolipoprotein B100 is added to VLDL in the __

liver

the apolipoproteins Apo-Cii and Apo-E come from __

HDL

What is the function of Apo-Cii in relation to VLDL?

-Binds to and activates __ for hydrolysis of triglycerides

LPL

Following interaction with lipoprotein lipase, what happens to VLDL lipoproteins?

-they decrease in size, and are termed either VLDL remnants or ___-__ ___ (IDL)

intermediate density lipoproteins

What are the two possible fates of IDL lipoproteins?

1) ___ by hepatocytes

endocytosis

What are the two possible fates of IDL lipoproteins?

2) further removal of triglycerides by __ ___ __ (HTGL)

hepatic triglyceride lipase

The IDL that remain in the bloodstream give back Apo-E to HDL. These particles are now called __ and carry only B100, low levels of TG, Ch, and Che.

LDL

What is the function of LDL?

-Deliver __ to various tissues for use in the biosynthesis of hormones and cell membrane maintenance, among other processes

cholesterol

What percentage of LDL is returned to the liver?

60

60% of LDL is returned to the liver. Where does the rest go, and why?

-the rest (40%) delivers cholesterol to to other __ (hormones, etc)

tissues

What happens to LDL particles when they make their way into the tunica intima and are exposed

to reactive oxygen species?

they are oxidized (now Ox-LDL)

What cell engulf these Ox-LDL particles?

macrophages

across what receptor are the Ox-LDL taken in?

fatty acid translocase (FAT/CD36)

Overaccumulation of Ox-LDL can convert macrophages to __ ___

foam cells

Accumulation of foam cells causes __ ___ (one of the earliest signs of atherosclerosis)

fatty streaks

What is the purpose of HDL lipoproteins?

reverse cholesterol transport

What is the initial apolipoprotein for HDL?

Apo-A1

Where does the initial apolipoprotein for HDL come

from?

-Apo-A1 is synthesized both in __ and by the ___

liver, intestine

Where do the phospholipids come from that make up HDL?

-they come from the surface layers of __ and __ during lipolysis

chylomicrons, VLDL

What is free cholesterol transported into and how?

-it is transported into immature HDL particle called prebeta-1 HDL through __ and __

ABCA1, ABCG1

How is cholesterol stored?

in cholesteryl ester

What enzyme is responsible for conversion of free cholesterol into cholesteryl ester?

-by Lecithin:cholesterol acetyl transferase (___)

LCAT

What protein allows for the transfer of stored cholesterol to VLDL, IDL, LDL, and chylomicron

particles?

cholesterol ester transfer protein (CETP)

What receptor do HDL lipoproteins bind to in order to deliver cholesterol to various targets?

SR-B1

Does HDL lipoproteins binding to SR-B1 in order to deliver cholesterol to various targets cause degredation of the HDL particles?

no

List the three categories of ___ dyslipidemias

1) hypertriglyceridemia

2) hypercholesterolemia

3) mixed hypercholesterolemia + hypertriglyceridemia

primary

1) hypertriglyceridemia is caused by elevated TG, secondary to increase in what 2 triglyceride rich lipoproteins?

VLDL, chylomicrons

1) hypertriglyceridemia

-can be caused by deficiency of ___-__ or __

apo-Cii, LPL

1) hypertriglyceridemia

c) can have unknown cause, which is then called __ ___

familial hypertriglyceridemia

2) hypercholesterolemias is characterized by elevated cholesterol and involves mutations in either the genes for the __ __ or for __-__

LDL receptor, apo-B100

2) hypercholesterolemias

a) can be ____ ___, which is when the cause is unknown

familial hypercholesterolemia

3) mixed hypercholesterolemia + hypertriglyceridemia

-familial dysbetalipoproteinemia or familial combined hyperlipidemia

-caused by mutation in ___ gene

ApoE

Causes of __ dyslipidemia:

-obesity

-diabetes

-hypothyroidism

-nephrotic syndrome

-alcohol, smoking

-meds (corticosteroids, thiazide diuretics, beta blockers, oral contraceptives)

secondary

How do the causes of secondary dyslipidemia impact lipoprotein metabolism?

-obesity increases serum levels of __ and ___

VLDL, chylomicrons

How do the causes of secondary dyslipidemia impact lipoprotein metabolism?

-the decreased insulin/insulin-resistance for patients with diabetes decreases efficiency of ____, which increases TG and VLDL/LDL

LPL

How do the causes of secondary dyslipidemia impact lipoprotein metabolism?

-hypothyroidism causes decreased T3/T4, which increases ___

LDL

How do the causes of secondary dyslipidemia impact lipoprotein metabolism?

-nephrotic syndrome- ____ increases VLDL and LDL

hypoalbuminemia

What are the main complications of uncontrolled hyperlipidemia?

1) atherosclerosis

2) pancreatitis

3) ___ ("fatty liver")

4) other complications like xanthomas, xanthelasma, corneal arcus, etc

steatosis

Cholesterol is an important structural component of ___ ___

cell membranes

Cholesterol is the starting material to synthesize ___ hormones

steroid

Cholesterol is the starting material to synthesize steroid hormones like glucocorticoids, which suppress ___

inflammation

Cholesterol is the starting material to synthesize steroid hormones like mineralocorticoids (eg aldosterone), which control __ __

blood pressure

Cholesterol is also the starting material to synthesize __ __

bile acids

Bile acids/bile salts play a key role in the digestion/absorption of __ and fat-soluble vitamins (from the diet) in the small intestine

fats

the bile acid cycle, also called enterohepatic circulation, involves bile acids being ___ into the ileum, returning to the liver via the portal vein, and being re-secreted into bile

reabsorbed

Bile acids help regulate ___ blood levels!

cholesterol

Bile acids help regulate cholesterol blood levels! namely by promoting the breakdown of cholesterol, which is eliminates from the body either as free __ or as __ __

cholesterol, bile acid

5% of bile salts are __ in the feces-- this is cholesterol disguised as a bile salt

lost

elevated blood levels of cholesterol increase risk of ____ (formation of plaque in arteries)

atherosclerosis

atherosclerosis is asymptomatic, but leads to ASCVD, which includes:

1) myocardial infarction (heart attack)

2) stroke

3) ___ ischemic attack (mini stroke)

transient

atherosclerosis is asymptomatic, but leads to ASCVD, which includes:

4) stable ___

5) peripheral artery disease

angina

2 main sources of cholesterol

1) our __

2) de novo/from scratch biosynthesis of cholesterol in the ___ by hepatocytes

diet, liver

How can we lower blood levels of cholesterol?

1) block absorption of cholesterol from diet into the blood stream by using ___

ezetimibe

How can we lower blood levels of cholesterol?

2) inhibit de novo synthesis of cholesterol by using __

statins

How can we lower blood levels of cholesterol?

3) block the enterohepatic circulation of bile acids to increase removal of cholesterol by using ____ ___ ___ (BAS)

bile acid sequestrants

VLDL are composed primarily of ____ and ultimately become LDL

triglycerides

LDL (bad cholesterol) are the number one driver of ___

atherosclerosis

HDL (good cholesterol) removes excess ___ from the tissues and arteries and returns it to liver for disposal

cholesterol

statins are grouped by ___ based on their LDL-lowering ability. Patients are categorized into statin benefit groups to determine the appropriate statin intensity

intensity

what is the enzyme that catalyzes the rate-limiting step in synthesis of cholesterol?

HMG CoA reductase

statins bind tightly to, and strongly ___ HMG-CoA reductase

inhibit

HMG-CoA reductase normally breaks the carbon-___ bond in the synthesis of cholesterol

sulfur

all HMG-CoA reductase inhibitors (including statins) are able inhibit the enzyme because their carbon-___ bond cannot be broken

carbon

statins all have an ionized ___ ___

carboxylic acid

Prodrugs are not active inhibitors of HMG CoA reductase until their lactone ring undergos in vivo hydrolysis to ionize the carboxylic acid. What statins are prodrugs?

lovastatin, simvastatin

the ionized carboxylic acid on statins forms a key __ anchoring interaction with positively charged ions within the active site of HMG CoA reductase

ionic

in addition to inhibiting cholesterol synthesis, statins will upregulate the number of ___ ___ on hepatocytes

LDL receptors

statins upregulate the number of LDL receptors on hepatocytes, which ultimately increases ___ of LDL from the blood into the liver

clearance

what are the statins going from most potent--> least potent (pharmacists rock at saving lives and preventing flu)

pitavastatin, rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, fluvastatin

since simvastatin and lovastatin are lactone prodrugs, they have very ___ half lives

short

due to the short half-lives of simvastatin and lovastatin, they should be taken at ___ because maximum de novo cholesterol synthesis happens between 12Am-2Am

bedtime

pitavastatin, rosuvastatin, atorvastatin, pravastatin, fluvastatin are active HMG-CoA reductase inhibitors (ie not prodrugs) and have ___ half lives

longer

in general, the statins with longer half lives can be taken at __ time of day

any

important patient counseling for statins includes describing symptoms of ___ __ (#1 adverse effect)

muscle damage

What does SAMS stand for?

statin associated muscle symptoms

SAMS usually presents as muscle soreness, tiredness, or weakness that is ___ (on both sides of body) in __ muscle groups (legs, back, arms)

symmetrical, large

SAMS can develop at ANY time during statin use, but are usually within __ weeks of starting treatment

6

there is increased risk of muscle effects with statins when used with

1) ____

2) more than 1g of __

fibrates, niacin

what is the term for muscle soreness and tenderness?

myalgia

___ ___ (CPK): a marker of damage of creatinine kinase-rich tissue, such as heart muscle tissue in myocardial infarction

creatinine phosphokinase

what is the term for muscle weakness with or without increased CPK?

myopathy